Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea.
Statistics Team, APACE, Seoul, Republic of Korea.
Clin Ther. 2024 Nov;46(11):870-876. doi: 10.1016/j.clinthera.2024.08.006. Epub 2024 Sep 16.
A fixed-dose combination (FDC) of proton pump inhibitors (PPIs) and antacid salts enables rapid acid suppression through the neutralizing effect of the antacid salt and the rapid absorption of PPIs. This study aimed to compare the pharmacokinetics (PKs) and pharmacodynamics (PDs) of a recently formulated FDC of esomeprazole and magnesium hydroxide to the enteric-coated esomeprazole in healthy subjects.
A randomized, open-label, multiple-dose, two-treatment, two-way crossover design was conducted in healthy subjects. Forty-nine subjects were randomized to one of the two treatment sequences and received either the test drug (esomeprazole/magnesium hydroxide 40/350 mg) or reference drug (enteric-coated esomeprazole 40 mg) for 7 days in the first period and the alternative in the second period with a 14-day washout period. Blood samples were collected for up to 24 hours for PK assessment, and 24-hour gastric pH monitoring was conducted for PD assessment both before and after a single administration, as well as at a steady state after seven consecutive days of administration. The PK and PD parameters were compared between the two drugs.
After multiple administrations, the median value of time to reach maximum concentration was faster in the test drug than in the reference drug, with a difference of 1.68 hours. The overall systemic exposure of the test drug was similar to that of the reference drug, and the PK parameter fell within the equivalence criteria. The test drug demonstrated a shorter time to reach gastric pH ≥ 4 compared to the reference drug (P = 0.0463). A decrease from baseline in integrated gastric acidity over 24 hours, which represents the degree of inhibition of gastric acid secretion, was equivalent between the two drugs.
The fixed-dose combination of esomeprazole and magnesium hydroxide showed rapid absorption and quicker gastric acid suppression than enteric-coated esomeprazole with comparable PK and PD properties.
gov identifier: NCT04324905 (https://classic.
gov/ct2/show/NCT04324905).
质子泵抑制剂（PPIs）和抗酸盐的固定剂量组合（FDC）通过抗酸盐的中和作用和 PPIs 的快速吸收实现快速酸抑制。本研究旨在比较最近配方的埃索美拉唑和氢氧化镁 FDC 与肠溶埃索美拉唑在健康受试者中的药代动力学（PK）和药效动力学（PD）。
在健康受试者中进行了一项随机、开放标签、多剂量、两治疗、两交叉设计的研究。49 名受试者随机分为两种治疗序列中的一种，在第一期分别接受试验药物（埃索美拉唑/氢氧化镁 40/350mg）或参比药物（肠溶埃索美拉唑 40mg）治疗 7 天，第二期接受替代药物治疗，洗脱期为 14 天。在单次给药前后以及连续给药 7 天后的稳态时，进行长达 24 小时的血样采集以进行 PK 评估和 24 小时胃 pH 监测。比较两种药物的 PK 和 PD 参数。
多次给药后，试验药物达到最大浓度的中位时间快于参比药物，相差 1.68 小时。试验药物的总体全身暴露与参比药物相似，PK 参数符合等效性标准。试验药物达到胃 pH≥4 的时间短于参比药物（P=0.0463）。与参比药物相比，24 小时内胃酸综合酸度从基线下降（代表胃酸分泌抑制程度）在两种药物之间相当。
埃索美拉唑和氢氧化镁的固定剂量组合与肠溶埃索美拉唑相比，显示出快速吸收和更快的胃酸抑制作用，具有相似的 PK 和 PD 特性。
gov 标识符：NCT04324905（https://classic.
gov/ct2/show/NCT04324905）。
